In this proposal we will investigate three aspects of iron metabolism during development using the rat as an experimental model. 1. We will determine the sequence of blood and tissue abnormalities when iron deficiency develops rapidly or slowly at various stages of early development. 2. We wish to determine whether hematopoiesis during early development is limited by the supply of iron when dietary intakes of iron are within the "physiologic" range and whether hematopoiesis can be further stimulated by pharmacologic doses of iron. We plan to administer increased amounts of oral and parenteral iron to young rats to determine whether the usual developmental changes in concentration of hemoglobin and red cell size can be modified by artificially maintaining an elevated concentration of serum iron. The studies should help to distinguish whether these developmental changes are attributable to iron-sulfur compounds and other constituents in mitochondria of skeletal muscle, heart, liver, and brain. The temporal sequence of changes in the various forms of heme iron, iron-sulfur centers, and other iron-proteins during the progression of iron deficiency and its subsequent reversal by the control diet will be delineated. We also wish to determine whether any particular change in mitochondrial composition is associated with a corresponding change in function. Such findings will be related to other aspects of iron metabolism in the animal, including the rate of depletion and repletion of ferritin stores, and to alterations in concentration of hemoglobin and myoglobin. We anticipate that the results will provide information regarding normal developmental changes and the pathogenesis of iron deficiency that cannot readily be obtained in man.